The theme of this center grant is the biochemical, molecular and exposure mechanisms that define children's susceptibility to pesticides: implications for assessing pesticide risks to normal development and learning. Consistent with the objectives of the RFA, we have designed a multi-disciplinary research center that takes advantages of the established landscape of risk research at the University of Washington. We have included members from multiple institutions, schools, and varied departments and clinics to facilitate both basic and applied research on reducing the adverse effects of environmental pesticide exposures. To achieve tangible effects on the community, we have partnered with an eastern Washington community within the Yakima Valley agricultural center of our state to jointly accomplish pesticide intervention with reduced childhood pesticide exposures. We have designed two laboratory based research projects and two field based projects which include an exposure pathways research project plus the related field based intervention study. The specific objectives of the laboratory based research projects will be to 1) identify cellular, biochemical and molecular mechanisms for the adverse developmental neurotoxicity of pesticides and 2) to identify the impact of genetic polymorphisms for paraoxonase on the developmental neurotoxicity of organophosphate pesticides. The specific objectives of the two field based projects are to 1) identify critical pathways of pesticide exposure for children and 2) to intervene to reduce children's exposure to pesticides. Our four facility cores (Neurobehavioral Assessment, Exposure Assessment, Risk Characterization and Risk Communication) have been designed to support this research agenda and to put our research into a child specific risk assessment context. Thus our scientific findings on pesticide toxicity and exposure can be directly incorporated into the risk assessment models we design to protect child health.